crossing96/oncoscreening huggingface dataset:
The Impact of Race and Sex on Metastatic Bladder Cancer Survival.	OBJECTIVE: To characterize the epidemiological profile of metastatic bladder cancer (BC) and assess mortality rate with respect to race and gender across the three most common histologies of bladder cancer-Transitional Cell Carcinoma, Adenocarcinoma, and SCC (Squamous Cell Carcinoma). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results Program database (2000-2017) was queried for all metastatic bladder cancer patients at presentation. Our primary exposure consists of four race/gender combinations. One-way ANOVA and Chi-square tests compared categorical and continuous variables across the exposure variable, respectively. Univariable and multivariable Cox proportional hazards regression analyses were used to examine the association between race/gender combinations and the overall and cancer specific survival adjusting for the other variables. RESULTS: A total of 312,846 bladder cancer patients, 6337 with distant metastases and 11,446 with regional metastases were evaluated. Black female cancer specific survival in metastatic disease was disproportionally lower compared to all race/gender for Transitional Cell Carcinoma 4.3% (95% CI: 1.6-8.9), SCC 2.6% (95% CI: 0.2-11.8), and Adenocarcinoma 6.4% (0.4%-25%). In regional metastastatic disease, worse cancer specific mortality was associated with identifying as a Black Female (aHR 1.17, P = .023), SCC (aHR 1.8, P <.001), increasing age (aHR 1.3, P <.001), and poorly differentiated grade (aHR 2.01, P <.001). CONCLUSION: Black females experience excess mortality in overall and cancer oncologic outcomes in metastatic BC. Our findings contribute to the body of research warranting examination of the impact of social determinants of health and provider decisions on BC survivorship and contribute to physician decision making in the treatment and surveillance of bladder cancer.	bladder
Mumio (Shilajit) as a potential chemotherapeutic for the urinary bladder cancer treatment.	Mumio (Shilajit) is a traditional medicinal drug known and used for hundreds of years. Bladder cancer is one of the most common cancer types and better treatments are needed. This study analysed the in vitro effect of Mumio on urinary bladder cancer cells (T24 and 5637) in comparison to normal uroepithelial cells (SV-HUC1). Cytotoxicity of Mumio was analysed in these cell lines via MTT and real-time cell growth assays as well via the assessment of the cytoskeleton, apoptosis, and cell cycle. Mumio affected the viability of both cell types in a time and concentration dependent manner. We observed a selectivity of Mumio against cancer cells. Cell cycle and apoptosis analysis showed that Mumio inhibited G0/G1 or S phase cell cycle, which in turn induced apoptosis. Our results showed that Mumio was significantly more cytotoxic to urinary bladder cancer cells than to normal cells. These results are promising and indicate Mumio as a great candidate for urinary bladder cancer treatment and further investigations should be performed.	bladder
Jolkinolide B sensitizes bladder cancer to mTOR inhibitors via dual inhibition of Akt signaling and autophagy.	The monotherapy of mTOR inhibitors (mTORi) in cancer clinical practice has achieved limited success due to the concomitant activation of compensatory pathways, such as Akt signaling and cytoprotective autophagy. Thus, the combination of mTORi and the inhibitors of these pro-survival pathways has been considered a promising therapeutic strategy. Herein, we report the synergistic effects of a natural anti-cancer agent Jolkinolide B (JB) and mTORi (temsirolimus, rapamycin, and everolimus) for the effective treatment of bladder cancer. A mechanistic study revealed that JB induced a dual inhibition of Akt feedback activation and cytoprotective autophagy, potentiating the anti-proliferative efficacy of mTORi in both PTEN-deficient and cisplatin-resistant bladder cancer cells. Meanwhile, mTORi augmented the pro-apoptotic and pro-paraptotic effects of JB by reinforcing JB-activated endoplasmic reticulum stress and MAPK pathways. These synergistic mechanisms were related to cellular reactive oxygen species accumulation. Our study suggests that dual inhibition of Akt feedback activation and cytoprotective autophagy is an effective strategy in mTORi-based therapy, and JB + mTORi combination associated with multiple anti-cancer mechanisms and good tolerance in mouse models may serve as a promising treatment for bladder cancer.	bladder
Evaluation of lymphocyte-specific programmed cell death protein 1 receptor expression and cytokines in blood and urine in canine urothelial carcinoma patients.	Urothelial carcinoma (UC) is the most common urinary tumour in dogs. Despite a range of treatment options, prognosis remains poor in dogs. In people, breakthroughs with checkpoint inhibitors have established new standards of care for muscle-invasive bladder cancer patients and elevated levels of programmed cell death protein 1 (PD-1) suggest immune checkpoint blockade may be a novel target for therapy. The goal of this study was to determine if canine UC patients express elevated levels of lymphocyte-specific PD-1 and/or urinary cytokine biomarkers compared to healthy dogs. Paired blood and urine were evaluated in 10 canine UC patients, five cystitis patients and 10 control dogs for lymphocyte-specific PD-1 expression via flow cytometry and relative cytokine expression. In UC patients, PD-1 expression was significantly elevated on CD8(+) lymphocytes in urine samples. UC patients had a higher CD4:CD8 ratio in their urine compared to healthy dogs, however, there was no significant variation in the CD8:Treg ratio between any group. Cystitis patients had significantly elevated levels of CD4(+) T cells, CD8(+) T cells and Tregs in their blood samples compared to UC patients and healthy dogs. Cytokine analysis demonstrated significant elevations in urinary cytokines (granulocyte-macrophage colony-stimulating factor, interferon-gamma [IFN-γ], interleukin (IL)-2, IL-6 IL-7, IL-8 and IL-15, IP-10, KC-like, IL-18, monocyte chemoattractant protein-1 and tumour necrosis factor-alpha). Several of these cytokines have been previously correlated with both lymphocyte-specific PD-1 expression (IFN-γ, IL-2, IL-7 and IL-15) in muscle-invasive urothelial carcinoma in humans. Our results provide evidence of urinary lymphocyte PD-1 expression and future studies could elucidate whether veterinary UC patients will respond favourably to anti-PD-1 immune checkpoint inhibitor therapy.	bladder
AKT1/HK2 Axis-mediated Glucose Metabolism: A Novel Therapeutic Target of Sulforaphane in Bladder Cancer.	SCOPE: Metabolic disorder is a pivotal hallmark of cancer cells. Sulforaphane (SFN) is reported to improve lipid metabolism. However, the effect of SFN on glucose metabolism in bladder cancer remains unclear. Hence, the effect and underling mechanism is investigated. METHODS AND RESULTS: Biological samples from bladder cancer patients are collected, and also investigated using N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder cancer mice and bladder cancer cell lines. A novel glucose transport aberrant-independent aerobic glycolysis is found in bladder cancer patients, and the lower malignancy tissues have the more obvious abnormality. SFN strongly downregulates ATP production by inhibiting glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). Both in vitro cell culture and in bladder tumor mice, SFN weaken the glycolytic flux by suppressing multiple metabolic enzymes, including hexokinase 2 (HK2) and pyruvate dehydrogenase (PDH). Moreover, SFN decreases the level of AKT1 and p-AKT (ser473) , especially in low-invasive UMUC3 cells. The downregulation of ATP and HK2 by SFN is both reversed by AKT1 overexpression. CONCLUSIONS: SFN downregulates the unique glucose transport aberrant-independent aerobic glycolysis existed in bladder cancer via blocking the AKT1/HK2 axis and PDH expression.	bladder
Emerging Intraoperative Imaging Technologies in Urologic Oncology.	As surgical cases become more complex, intraoperative imaging is increasingly being used. This article discusses emerging imaging technologies used in prostate, kidney, and bladder cancer surgery, including ultrasound, fluorescence-based, and enhanced endoscopy techniques including their strengths and limitations.	bladder
Preoperative abdominal fat distribution and systemic immune inflammation were associated with response to intravesical Bacillus Calmette-Guerin immunotherapy in patients with non-muscle invasive bladder cancer.	OBJECTIVE: To investigate the predictors of response to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) patients. MATERIALS AND METHODS: We retrospectively analyzed the clinicopathological data of 184 intermediate and high risk NMIBC cases receiving transurethral resection of bladder tumor (TURBT) and intravesical BCG immunotherapy from December 2014 to April 2021 at our center. All patients were divided into BCG responders and non-responders. Multivariate Logistic regression analysis was performed to identify the independent predictors of response to intravesical BCG immunotherapy. Univariate and multivariate Cox regression analyses were applied to explore the independent prognostic factors of recurrence-free survival (RFS). Receiver operating characteristic (ROC) curve and Kaplan-Meier survival analysis were also utilized. RESULTS: The RFS of BCG responders was significantly increased compared with BCG non-responders. Multivariate Cox regression analysis demonstrated that low grade, pTa stage, non-CIS, lower relative visceral fat area (rVFA) and lower systemic immune inflammation index (SII) were independent prognostic factors of increased RFS after intravesical BCG immunotherapy. Multivariate Logistic regression analysis demonstrated that pTa stage, low grade, non-CIS, low rVFA, and low SII were independent predictors of response to intravesical BCG immunotherapy. Kaplan-Meier survival analysis indicated that the RFS of patients in low rVFA group or low SII group was significantly increased in comparison with those in high rVFA group or high SII group. ROC curve analysis showed that the area under ROC (AUC) of including SII and rVFA was significantly increased, indicating that the inclusion of preoperative SII and rVFA could significantly improve the predictive efficiency. CONCLUSIONS: Low grade, pTa stage, non-CIS, preoperative lower rVFA and lower SII were vital independent predictors of response to intravesical BCG immunotherapy and were associated with preferable prognosis in NMIBC patients. The inclusion of preoperative SII and rVFA could significantly improve the predictive efficiency.	bladder
Metabolomic credentialing of murine carcinogen-induced urothelial cancer.	Bladder cancer (BCa) is the most common malignancy of the urinary system with increasing incidence, mortality, and limited treatment options. Therefore, it is imperative to validate preclinical models that faithfully represent BCa cellular, molecular, and metabolic heterogeneity to develop new therapeutics. We performed metabolomic profiling of premalignant and non-muscle invasive bladder cancer (NMIBC) that ensued in the chemical carcinogenesis N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model. We identified the enriched metabolic signatures that associate with premalignant and NMIBC. We found that enrichment of lipid metabolism is the forerunner of carcinogen-induced premalignant and NMIBC lesions. Cross-species analysis revealed the prognostic value of the enzymes associated with carcinogen-induced enriched metabolic in human disease. To date, this is the first study describing the global metabolomic profiles associated with early premalignant and NMIBC and provide evidence that these metabolomic signatures can be used for prognostication of human disease.	bladder
Correlation between aryl hydrocarbon receptor and IL-17(+) and Foxp3(+) T-cell infiltration in bladder cancer.	Bladder cancer (BC) is one of the most prevalent cancers around the world and, if not treated well, has high morbidity and mortality. Many studies have indicated that there may be various roles for the aryl hydrocarbon receptor (AHR) in the immune system. The aim of this study was to determine the frequency of Foxp3(+) regulatory T (Treg) and T helper 17 cells (Th17) in BC tissue in comparison with controls and determine the relationship between AHR, Foxp3(+) Treg and Th17 cells in BC. A total of 40 patients with BC were enrolled in this study. The control group was selected from non-tumoural parts of bladder tissues from the patients who have undergone cystoscopy. The percentage of regulatory T cells (Foxp3(+) /CD4(+) ) and Th17 (IL-17(+) /CD4(+) ), as well as AHR(+) cells in BC tissues and controls, were determined by immunohistochemistry. The results of this study showed that the number of Foxp3(+) Treg and Th17 is significantly higher in bladder tumour tissues in comparison with non-tumoural tissues. Also, the percentage of AHR(+) lymphocytes and AHR(+) cells was increased significantly in bladder tumour tissues rather than non-tumoural tissues. This study also found a relation between AHR and Foxp3(+) /CD4(+) T lymphocytes ratio cells in BC. The percentage of Foxp3(+) Tregs and AHR(+) cells were significantly correlated with the grade and stage of BC. An increase in the percentage of Foxp3(+) Treg and Th17 cells may play an important role in tumour immunity; and determining the relationship between AHR and differentiation of Th17/Foxp3(+) Treg in BC can lead to a potential cancer therapeutic possibility.	bladder
Supportive Roles of the Health Care Team Throughout the Illness Trajectory of Bladder Cancer Patients Undergoing Radical Cystectomy: A Qualitative Study Exploring the Patients' Perspectives.	OBJECTIVES: To explore patient perspectives of muscle-invasive bladder cancer (MIBC) on how the health care team and their social network can support them during their cancer trajectory. DATA SOURCES: Sixteen semi-structured interviews were conducted with MIBC survivors who underwent radical cystectomies at Ghent University Hospital. The interviews were audiotaped, transcribed verbatim, and analyzed with an iterative content analysis approach. CONCLUSION: Information to support people affected by bladder cancer (BC) in several aspects of their disease trajectory (eg, shared decision-making and self-management of their urinary diversion) was most important throughout the interviews (although type and source of required information varied). The clinical nurse specialist was important for informational and emotional support because receiving sufficient information might help patients reduce emotional stress. People affected by BC are still reluctant to consult a psychologist, and several barriers were indicated for this. Also physical needs in the early postoperative phase could be reduced with appropriate information. Communication skills of clinicians in the hospital and knowledge of general practitioners about the important aspects of BC care are also important aspects that should be further optimized. Furthermore, peer support groups and family members can offer important support throughout the BC pathway. IMPLICATIONS FOR NURSING PRACTICE: This study provides an overview of how people affected by BC want to be supported by their health care team and their social network. This overview can serve as a basis to develop educational interventions for both patients and health care professionals to guide restructuring of BC pathways and can also be used to develop future intervention studies to improve BC outcomes.	bladder
Diagnostic Accuracy of Novel Urinary Biomarker Tests in Non-muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis.	CONTEXT: During the past decade, several urinary biomarker tests (UBTs) for bladder cancer have been developed and made commercially available. However, none of these is recommended by international guidelines so far. OBJECTIVE: To assess the diagnostic estimates of novel commercially available UBTs for diagnosis and surveillance of non-muscle-invasive bladder cancer (NMIBC) using diagnostic test accuracy (DTA) and network meta-analysis (NMA). EVIDENCE ACQUISITION: PubMed, Web of Science, and Scopus were searched up to April 2021 to identify studies addressing the diagnostic values of UBTs: Xpert bladder cancer, Adxbladder, Bladder EpiCheck, Uromonitor and Cxbladder Monitor, and Triage and Detect. The primary endpoint was to assess the pooled diagnostic values for disease recurrence in NMIBC patients using a DTA meta-analysis and to compare them with cytology using an NMA. The secondary endpoints were the diagnostic values for high-grade (HG) recurrence as well as for the initial detection of bladder cancer. EVIDENCE SYNTHESIS: Twenty-one studies, comprising 7330 patients, were included in the quantitative synthesis. In most of the studies, there was an unclear risk of bias. For NMIBC surveillance, novel UBTs demonstrated promising pooled diagnostic values with sensitivities up to 93%, specificities up to 84%, positive predictive values up to 67%, and negative predictive value up to 99%. Pooled estimates for the diagnosis of HG recurrence were similar to those for the diagnosis of any-grade recurrence. The analysis of the number of cystoscopies potentially avoided during the follow-up of 1000 patients showed that UBTs might be efficient in reducing the number of avoidable interventions with up to 740 cystoscopies. The NMA revealed that diagnostic values (except specificity) of the novel UBTs were significantly higher than those of cytology for the detection of NMIBC recurrence. There were too little data on UBTs in the primary diagnosis setting to allow a statistical analysis. CONCLUSIONS: Our analyses support high diagnostic accuracy of the studied novel UBTs, supporting their utility in the NMIBC surveillance setting. All of these might potentially help prevent unnecessary cystoscopies safely. There are not enough data to reliably assess their use in the primary diagnostic setting. These results have to be confirmed in a larger cohort as well as in head-to-head comparative studies. Nevertheless, our study might help policymakers and stakeholders evaluate the clinical and social impact of the implementation of these tests into daily practice. PATIENT SUMMARY: Novel urinary biomarker tests outperform cytology with the potential of improving routine clinical practice by preventing unnecessary cystoscopic examinations during the surveillance of non-muscle-invasive bladder cancer.	bladder
Diffusive Ki67 and vimentin are associated with worse recurrence-free survival of upper tract urothelial carcinoma: A retrospective cohort study from bench to bedside.	OBJECTIVES: This study aimed to determine the prognostic values of Ki67 and vimentin in upper tract urothelial carcinoma (UTUC) after extirpative surgery. METHODS AND MATERIALS: Between 2014 and 2019, patients diagnosed with UTUC and receiving radical nephroureterectomy were included retrospectively. Nuclear MIB-1 clones and cytoplasmic VIM 3B4 clones were used to assess Ki67 and vimentin levels, respectively. A unified reading protocol was applied, and the expression level was read by a single pathologist. Receiver operating characteristic curves were utilized to determine the best threshold for Ki67 and vimentin regarding recurrence, and this level was set as the diffusive level. The outcome of recurrence-free survival (RFS) was analyzed via a Cox regression model with univariable and multivariable approaches. Survival outcomes were analyzed via Kaplan-Meier (KM) curves. RESULTS: A total of 247 patients were included, and the mean follow-up was 29.90 ± 6.80 months. Diffusive thresholds were 17.5% for both Ki67 and vimentin. Under multivariable Cox regression, diffusive Ki67 (hazard ratio: 4.20 [2.39-7.37], P < 0.001) and diffusive vimentin (hazard ratio: 5.34 [3.10-9.22], P < 0.001) were significant prognostic indicators of worse RFS. Diffusive Ki67 was accompanied by diffusive vimentin (chi square with Yates' correction, P = 0.015), and vice versa. In the KM curve, there was no difference between diffusive Ki67/nondiffusive vimentin and nondiffusive Ki67/diffusive vimentin (log-rank test, P = 0.073). Significant differences (log-rank test, P < 0.001) were seen in different combinations of diffusive Ki67/vimentin (Mean RFS: 19.76 [18.56-20.96] months), only one diffusive in Ki67 or vimentin (Mean RFS: 22.94 [21.88-24.00] months), and nondiffusive Ki67/vimentin (Mean RFS: 32.96 [32.43-33.50] months). CONCLUSIONS: Diffusive Ki67 and vimentin were related to each other, and they exerted equivalent and synergic effects on predicting worse RFS in UTUC.	bladder
Concomitant robot-assisted laparoscopic surgeries for upper and lower urinary tract malignancies: a comprehensive literature review.	Worldwide, we have witnessed an expansion of robot-assisted laparoscopic surgery (RALS) and thanks to the global adoption of high-resolution diagnostic imaging technologies, an increased incidence of newly diagnosed prostatic, renal and bladder cancers has been recorded with concurrent second primary urological cancer diagnoses increasing by 1.5%. Diverse authors have reported their findings concerning synchronous multi-visceral malignances robotic treatment within the scientific literature. The aim of this study is to comprehensively review all reported articles describing concurrent upper and lower RALS using a singular robotic port scheme within the same intervention for renal malignances and concomitant prostatic or bladder cancers. To the best of our knowledge and vigorous literature search, this is the first study that comprehensively evaluates and reports all combined upper and lower urinary tract surgeries published so far. In carefully selected patients, thanks to multidisciplinary preoperative assessment and surgical planning a combined robotic approach can reduce the morbidity, complications, hospital admissions and the overall length of hospitalization.	bladder
The role of TAp63γ and P53 point mutations in regulating DNA repair, mutational susceptibility and invasion of bladder cancer cells.	It has long been recognized that non-muscle-invasive bladder cancer (NMIBC) has a low propensity (20%) of becoming muscle-invasive (MIBC), and that MIBC carry many more p53 point mutations (p53m) than NMIBC (50% vs 10%). MIBC also has a higher mutation burden than NMIBC. These results suggest that DNA repair capacities, mutational susceptibility and p53m are crucial for MIBC development. We found MIBC cells are hypermutable, deficient in DNA repair and have markedly downregulated DNA repair genes, XPC, hOGG1/2 and Ref1, and the tumor suppressor, TAp63γ. In contrast, NMIBC cells are hyperactive in DNA repair and exhibit upregulated DNA repair genes and TAp63γ. A parallel exists in human tumors, as MIBC tissues have markedly lower DNA repair activity, and lower expression of DNA repair genes and TAp63γ compared to NMIBC tissues. Forced TAp63γ expression in MIBC significantly mitigates DNA repair deficiencies and reduces mutational susceptibility. Knockdown of TAp63γ in NMIBC greatly reduces DNA repair capacity and enhances mutational susceptibility. Manipulated TAp63γ expression or knockdown of p53m reduce the invasion of MIBC by 40-60%. However, the combination of p53m knockdown with forced TAp63γ expression reduce the invasion ability to nil suggesting that p53m contributes to invasion phenotype independent from TAp63γ. These results indicate that in BC, TAp63γ regulates DNA repair capacities, mutational susceptibility and invasion, and that p53m contribute to the invasion phenotype. We conclude that concurrent TAp63γ suppression and acquisition of p53m are a major cause for MIBC development.	bladder